Somatomedins or Insulin-Like Growth Factors are a group of polypeptides which are potent mitogens for many cell lines and which also possess insulin-like activities in extraskeletal tissues. The structure of one of these growth factors, the Insulin-Like Growth Factor I (IGF-I) has been recently elucidated and found to have a striking homology to proinsulin. The supply of somatomedins by isolation from natural sources is extremely limited and hence their precise role in normal physiology and in pathological states is not defined. It is one of the goals of this investigation to chemically synthesize IGF-I and make it available for in vitro and long-term in vivo studies so that we may gain a greater understanding of the physiological role of these factors. A second aim of this investigation is the elucidation of the relationship between chemical structure and biological activity of IGF-I by the synthesis of a variety of analogs embodying structural features found in both IGF-I and insulin. This last aspect of the proposed studies may lead to the synthesis of new "insulin-like" compounds and may help to delineate the regions of the IGF-I molecule responsible for the insulin-like effects and the growth-promoting effects. Successful outcome of the latter studies may lead to the synthesis of "tailor-made" compounds possessing insulin-like and/or growth-promoting activities.